New disease

BMJ Case Rep: first published as 10.1136/bcr-2020-235920 on 24 August 2020. Downloaded from http://casereports.bmj.com/ on June 4, 2024 by guest. Protected by copyright.
Case report

Clinical course of a 66-year-old man with an acute

ischaemic stroke in the setting of a
COVID-19 infection
Saajan Basi ,1,2 Mohammad Hamdan,1 Shuja Punekar1

1
Department of Stroke and SUMMARY positive cases from 604 COVID-19 tests conducted
Acute Medicine, King’s Mill A 66-year-old man was admitted to hospital with a right in the local community, with a predicted population
Hospital, Sutton-in-Ashfield, UK frontal cerebral infarct producing left-sided weakness of 108 000.4 Only 4 days later, when this patient
2
Department of Acute Medicine, died, the figure increased to 172 positive cases (81%
and a deterioration in his speech pattern. The cerebral
University Hospitals of Derby
infarct was confirmed with CT imaging. The only increase), illustrating the rapid escalation towards
and Burton, Derby, UK
evidence of respiratory symptoms on admission was a 2 the peak of the pandemic, and widespread transmis-
Correspondence to L oxygen requirement, maintaining oxygen saturations sion within the local community (figure 1). As more
Dr Saajan Basi; between 88% and 92%. In a matter of hours this patient cases of ischaemic stroke in COVID-19 pneumonia
saajan.basi@nhs.net developed a greater oxygen requirement, alongside patients arise, the recognition and understanding
reduced levels of consciousness. A positive COVID-19 of its presentation and aetiology can be deci-
Accepted 15 July 2020 throat swab, in addition to bilateral pneumonia on chest phered. Considering the virulence of SARS-CoV-2
X-ray and lymphopaenia in his blood tests, confirmed a it is crucial as a global healthcare community, we
diagnosis of COVID-19 pneumonia. A proactive decision develop this understanding, in order to intervene
was made involving the patients’ family, ward and and reduce significant morbidity and mortality in
intensive care healthcare staff, to not escalate care above stroke patients.
a ward-based ceiling of care. The patient died 5 days
following admission under the palliative care provided by
the medical team. CASE PRESENTATION
A 66-year-old man presented to the hospital with
signs of left-sided weakness. The patient had a
background of chronic obstructive pulmonary
BACKGROUND disease (COPD), atrial fibrillation and had one
SARS-CoV-2 (Severe Acute Respiratory Syndrome previous ischaemic stroke, producing left-sided
Coronavirus 2) is a new strain of coronavirus that haemiparesis, which had completely resolved. He
is thought to have originated in December 2019 in was a non-smoker and lived in a house. The patient
Wuhan, China. In a matter of months, it has erupted was found slumped over on the sofa at home on 1
from non-existence to perhaps the greatest chal- April 2020, by a relative at approximately 01:00,
lenge to healthcare in modern times, grinding most having been seen to have no acute medical illness
societies globally to a sudden halt. Consequently, the at 22:00. The patients’ relative initially described
study and research into SARS-CoV-2 is invaluable. disorientation and agitation with weakness noted
Although coronaviruses are common, SARS-CoV-2 in the left upper limb and dysarthria. At the time
appears to be considerably more contagious. The of presentation, neither the patient nor his relative
WHO figures into the 2003 SARS-CoV-1 outbreak, identified any history of fever, cough, shortness of
from November 2002 to July 2003, indicate a breath, loss of taste, smell or any other symptoms;
total of 8439 confirmed cases globally.1 In compar- however, the patient did have a prior admission 9
ison, during a period of 4 months from December days earlier with shortness of breath.
2019 to July 2020, the number of global cases of The vague nature of symptoms, entwined with
COVID-19 reached 10 357 662, increasing expo- considerable concern over approaching the hospital,
nentially, illustrating how much more contagious due to the risk of contracting COVID-19, created
SARS-CoV-2 has been.2 a delay in the patients’ attendance to the accident
Previous literature has indicated infections, and and emergency department. His primary survey
© BMJ Publishing Group influenza-like illness have been associated with an conducted at 09:20 on 1 April 2020 demonstrated
Limited 2020. Re-use overall increase in the odds of stroke development.3 a patent airway, with spontaneous breathing and
permitted under CC BY-NC. No
commercial re-use. See rights
There appears to be a growing correlation between good perfusion. His Glasgow Coma Scale (GCS)
and permissions. Published COVID-19 positive patients presenting to hospital score was 15 (a score of 15 is the highest level of
by BMJ. with ischaemic stroke; however, studies investi- consciousness), his blood glucose was 7.2, and he
gating this are in progress, with new data emerging did not exhibit any signs of trauma. His abbrevi-
To cite: Basi S, Hamdan M,
Punekar S. BMJ Case daily. This patient report comments on and further ated mental test score was 7 out of 10, indicating
Rep 2020;13:e235920. characterises the link between COVID-19 pneu- a degree of altered cognition. An ECG demon-
doi:10.1136/bcr-2020- monia and the development of ischaemic stroke. At strated atrial fibrillation with a normal heart rate.
235920 the time of this patients’ admission, there were 95 His admission weight measured 107 kg. At 09:57
Basi S, et al. BMJ Case Rep 2020;13:e235920. doi:10.1136/bcr-2020-235920 1
 New disease

BMJ Case Rep: first published as 10.1136/bcr-2020-235920 on 24 August 2020. Downloaded from http://casereports.bmj.com/ on June 4, 2024 by guest. Protected by copyright.
Figure 3 Chest X-ray demonstrating the bilateral COVID-19
Figure 1 A graph showing the number of patients with COVID-19 in pneumonia of this patient on admission.
the hospital and in the community over time.

acute cerebral infarction. An erect AP chest X-ray with portable

the patient required 2 L of nasal cannula oxygen to maintain equipment (figure 3) conducted on the same day demonstrated
his oxygen saturations between 88% and 92%. He started to patchy peripheral consolidation bilaterally, with no evidence of
develop agitation associated with an increased respiratory rate at significant pleural effusion. The pattern of lung involvement
36 breaths per minute. On auscultation of his chest, he demon- raised suspicion of COVID-19 infection, which at this stage
strated widespread coarse crepitation and bilateral wheeze. was thought to have provoked the acute cerebral infarct. Clini-
Throughout he was haemodynamically stable, with a systolic cally significant blood results from 1 April 2020 demonstrated a
blood pressure between 143 mm Hg and 144 mm Hg and heart raised C-reactive protein (CRP) at 215 mg/L (normal 0–5 mg/L)
rate between 86 beats/min and 95 beats/min. From a neurolog- and lymphopaenia at 0.5×109 (normal 1×109 to 3×109). Other
ical standpoint, he had a mild left facial droop, 2/5 power in routine blood results are provided in table 1.
both lower limbs, 2/5 power in his left upper limb and 5/5 power Interestingly the patient, in this case, was clinically assessed in
in his right upper limb. Tone in his left upper limb had increased. the accident and emergency department on 23 March 2020, 9
This patient was suspected of having COVID-19 pneumonia days prior to admission, with symptoms of shortness of breath.
alongside an ischaemic stroke. His blood results from this day showed a CRP of 22 mg/L
and a greater lymphopaenia at 0.3×109. He had a chest X-ray
INVESTIGATIONS (figure 4), which indicated mild radiopacification in the left
A CT of his brain conducted at 11:38 on 1 April 2020 (figure 2) mid zone. He was initially treated with intravenous co-amox-
illustrated an ill-defined hypodensity in the right frontal lobe iclav and ciprofloxacin. The following day he had minimal
medially, with sulcal effacement and loss of grey-white matter. symptoms (CURB 65 score 1 for being over 65 years). Given
This was highly likely to represent acute anterior cerebral artery improving blood results (declining CRP), he was discharged
territory infarction. Furthermore an oval low-density area in home with a course of oral amoxicillin and clarithromycin. As
the right cerebellar hemisphere, that was also suspicious of national governmental restrictions due to COVID-19 had not
an acute infarction. These vascular territories did not entirely
correlate with his clinical picture, as limb weakness is not as
prominent in anterior cerebral artery territory ischaemia. There- Table 1 Clinical biochemistry and haematology blood results of the
fore this left-sided weakness may have been an amalgamation of patient
residual weakness from his previous stroke, in addition to his Hb 157 g/L
WCC 5.8
Platelet count 195
MCV 86
Neutrophils 4.9
Lymphocytes 0.5
INR 1.3
PT 16.7
APTT 28
Sodium 137
Potassium Sample haemolysed
Urea 9.5
Creatinine 84
eGFR 83
Bilirubin 26
Albumin 29
CRP 215
Total protein 69
APTT, activated partial thromboplastin time; CRP, C-reactive protein; eGFR, estimated
Figure 2 CT imaging of this patients’ brain demonstrating a wedge- glomerular filtration rate; Hb, haemoglobin; INR, international normalised ratio; MCV,
shaped infarction of the anterior cerebral artery territory. mean corpuscular volume; PT, prothrombin time; WCC, white cell count.

2 Basi S, et al. BMJ Case Rep 2020;13:e235920. doi:10.1136/bcr-2020-235920

 New disease

BMJ Case Rep: first published as 10.1136/bcr-2020-235920 on 24 August 2020. Downloaded from http://casereports.bmj.com/ on June 4, 2024 by guest. Protected by copyright.
advocated by the stroke team. The patient was given 300 mg of
aspirin and was not a candidate for fibrinolysis.

OUTCOME AND FOLLOW-UP

The following day, before the throat swab result, had appeared
the patient deteriorated further, requiring 15 L of oxygen through
a non-rebreather face mask at 60% FiO2 to maintain his oxygen
saturation, at a maximum of 88% overnight. At this point, he
was unresponsive to voice, with a GCS of 5. Although, he was
still haemodynamically stable, with a blood pressure of 126/74
mm Hg and a heart rate of 98 beats/min. His respiratory rate was
30 breaths/min. His worsening respiratory condition, combined
with his declining level of consciousness made it impossible to
clinically assess progression of the neurological deficit generated
by his cerebral infarction. Moreover, the patient was declining
sharply while receiving the maximal ward-based treatment avail-
Figure 4 Chest X-ray conducted on prior admission illustrating mild able. The senior respiratory physician overseeing the patients’
radiopacification in the left mid zone. care decided that a palliative approach was in this his best
interest, which was agreed on by all parties. The respiratory team
completed the ‘recognising dying’ documentation, which signi-
fied that priorities of care had shifted from curative treatment
been formally announced until 23 March 2020, and inconsis- to palliative care. Although the palliative team was not formally
tencies regarding personal protective equipment training and involved in the care of the patient, the patient received comfort
usage existed during the earlier stages of this rapidly evolving measures without further attempts at supporting oxygenation,
pandemic, it is possible that this patient contracted COVID-19 or conduction of regular clinical observations. The COVID-19
within the local community, or during his prior hospital admis- throat swab confirmed a positive result on 2 April 2020. The
sion. It could be argued that the patient had early COVID-19 patient was treated by the medical team under jurisdiction of the
signs and symptoms, having presented with shortness of breath, hospital palliative care team. This included the prescribing of
lymphopaenia, and having had subtle infective chest X-ray anticipatory medications and a syringe driver, which was estab-
changes. The patient explained he developed a stagnant produc- lished on 3 April 2020. His antibiotic treatment, non-essential
tive cough, which began 5 days prior to his attendance to hospital medication and intravenous fluid treatment were discontinued.
on 23 March 2020. He responded to antibiotics, making a full His comatose condition persisted throughout the admission.
recovery following 7 days of treatment. This information does Once the patients’ GCS was 5, it did not improve. The patient
not assimilate with the typical features of a COVID-19 infec- was pronounced dead by doctors at 08:40 on 5 April 2020.
tion. A diagnosis of community-acquired pneumonia or infec-
tive exacerbation of COPD seem more likely. However, given
the high incidence of COVID-19 infections during this patients’ DISCUSSION
illness, an exposure and early COVID-19 illness, prior to the 23 SARS-CoV-2 is a type of coronavirus that was first reported to
March 2020, cannot be completely ruled out. have caused pneumonia-like infection in humans on 3 December
2019.5 As a group, coronaviruses are a common cause of upper
and lower respiratory tract infections (especially in children) and
TREATMENT have been researched extensively since they were first character-
On the current admission, this patient was managed with nasal ised in the 1960s.6 To date, there are seven coronaviruses that
cannula oxygen at 2 L. By the end of the day, this had progressed to are known to cause infection in humans, including SARS-CoV-1,
a venturi mask, requiring 8 L of oxygen to maintain oxygen satu- the first known zoonotic coronavirus outbreak in November
ration. He had also become increasingly drowsy and confused, 2002.7 Coronavirus infections pass through communities during
his GCS declined from 15 to 12. However, the patient was still the winter months, causing small outbreaks in local communi-
haemodynamically stable, as he had been in the morning. An ties, that do not cause significant mortality or morbidity.
arterial blood gas demonstrated a respiratory alkalosis (pH 7.55, SARS-CoV-2 strain of coronavirus is classed as a zoonotic coro-
pCO2 3.1, pO2 6.7 and HCO3 24.9, lactate 1.8, base excess 0.5). navirus, meaning the virus pathogen is transmitted from non-
He was commenced on intravenous co-amoxiclav and ciproflox- humans to cause disease in humans. However the rapid spread of
acin, to treat a potential exacerbation of COPD. This patient had SARS-CoV-2 indicates human to human transmission is present.
a COVID-19 throat swab on 1 April 2020. Before the result of From previous research on the transmission of coronaviruses
this swab, an early discussion was held with the intensive care and that of SARS-CoV-2 it can be inferred that SARS-CoV-2
unit staff, who decided at 17:00 on 1 April 2020 that given the spreads via respiratory droplets, either from direct inhalation, or
patients presentation, rapid deterioration, comorbidities and indirectly touching surfaces with the virus and exposing the eyes,
likely COVID-19 diagnosis he would not be for escalation to the nose or mouth.8 Common signs and symptoms of the COVID-19
intensive care unit, and if he were to deteriorate further the end infection identified in patients include high fevers, severe fatigue,
of life pathway would be most appropriate. The discussion was dry cough, acute breathing difficulties, bilateral pneumonia on
reiterated to the patients’ family, who were in agreement with radiological imaging and lymphopaenia.9 Most of these features
this. Although he had evidence of an ischaemic stroke on CT were identified in this case study. The significance of COVID-19
of his brain, it was agreed by all clinicians that intervention for is illustrated by the speed of its global spread and the potential
this was not as much of a priority as providing optimal palliative to cause severe clinical presentations, which as of April 2020 can
care, therefore, a minimally invasive method of treatment was only be treated symptomatically. In Italy, as of mid-March 2020,
Basi S, et al. BMJ Case Rep 2020;13:e235920. doi:10.1136/bcr-2020-235920 3
 New disease

BMJ Case Rep: first published as 10.1136/bcr-2020-235920 on 24 August 2020. Downloaded from http://casereports.bmj.com/ on June 4, 2024 by guest. Protected by copyright.
it was reported that 12% of the entire COVID-19 positive popu- If we delve further into this patients’ comorbid state exclu-
lation and 16% of all hospitalised patients had an admission to sive to COVID-19 infection, it can be argued that this patient
the intensive care unit.10 was already at a relatively higher risk of stroke development
The patient, in this case, illustrates the clinical relevance of compared with the general population. The fact this patient had
understanding COVID-19, as he presented with an ischaemic previously had an ischaemic stroke illustrates a prior suscepti-
stroke underlined by minimal respiratory symptoms, which bility. This patient had a known background of hypertension and
progressed expeditiously, resulting in acute respiratory distress atrial fibrillation, which as mentioned previously, can influence
syndrome and subsequent death. blood clot or plaque propagation in the development of an acute
Our case is an example of a new and ever-evolving clinical ischaemic event.15 Although the patient was prescribed rivarox-
correlation, between patients who present with a radiological aban as an anticoagulant, true consistent compliance to rivar-
confirmed ischaemic stroke and severe COVID-19 pneumonia. oxaban or other medications such as amlodipine, clopidogrel,
As of April 2020, no comprehensive data of the relationship candesartan and atorvastatin cannot be confirmed; all of which
between ischaemic stroke and COVID-19 has been published, can contribute to the reduction of influential factors in the devel-
however early retrospective case series from three hospitals in opment of ischaemic stroke. Furthermore, the fear of contracting
Wuhan, China have indicated that up to 36% of COVID-19 COVID-19, in addition to his vague symptoms, unlike his prior
patients had neurological manifestations, including stroke.11 ischaemic stroke, which demonstrated dense left-sided haemi-
These studies have not yet undergone peer review, but they tell paresis, led to a delay in presentation to hospital. This made
us a great deal about the relationship between COVID-19 and treatment options like fibrinolysis unachievable, although it
ischaemic stroke, and have been used to influence the Amer- can be argued that if he was already infected with COVID-
ican Heart Associations ‘Temporary Emergency Guidance to US 19, he would have still developed life-threatening COVID-19
Stroke Centres During the COVID-19 Pandemic’.12 pneumonia, regardless of whether he underwent fibrinolysis. It
The relationship between similar coronaviruses and other is therefore important to consider that if this patient did not
viruses, such as influenza in the development of ischaemic stroke contract COVID-19 pneumonia, he still had many risk factors
has previously been researched and provide a basis for further that made him prone to ischaemic stroke formation. Thus, we
investigation, into the prominence of COVID-19 and its rela- must consider whether similar patients would suffer from isch-
tion to ischaemic stroke.3 Studies of SARS-CoV-2 indicate its aemic stroke, regardless of COVID-19 infection and whether
receptor-binding region for entry into the host cell is the same COVID-19 impacts on the severity of the stroke as an entity.
as ACE2, which is present on endothelial cells throughout the Having said this, the management of these patients is depen-
body. It may be the case that SARS-CoV-2 alters the conventional dent on the likelihood of a positive outcome from the COVID-19
ability of ACE2 to protect endothelial function in blood vessels, infection. Establishing the ceiling of care is crucial, as it prevents
promoting atherosclerotic plaque displacement by producing incredibly unwell or unfit patients’ from going through futile
an inflammatory response, thus increasing the risk of ischaemic treatments, ensuring respect and dignity in death, if this is the
stroke development.13 likely outcome. It also allows for the provision of limited or
Other hypothesised reasons for stroke development in intensive resources, such as intensive care beds or endotracheal
COVID-19 patients are the development of hypercoagula- intubation during the COVID-19 pandemic, to those who are
bility, as a result of critical illness or new onset of arrhyth- assessed by the multidisciplinary team to benefit the most from
mias, caused by severe infection. Some case studies in Wuhan their use. The way to establish this ceiling of care is through an
described immense inflammatory responses to COVID-19, early multidisciplinary discussion. In this case, the patient did
including elevated acute phase reactants, such as CRP and not convey his wishes regarding his care to the medical team
D-dimer. Raised D-dimers are a non-specific marker of a or his family; therefore it was decided among intensive care
prothrombotic state and have been associated with greater specialists, respiratory physicians, stroke physicians and the
morbidity and mortality relating to stroke and other neuro- patients’ relatives. The patient was discussed with the intensive
logical features.14 care team, who decided that as the patient sustained two acute
Arrhythmias such as atrial fibrillation had been identified life-threatening illnesses simultaneously and had rapidly deterio-
in 17% of 138 COVID-19 patients, in a study conducted in rated, ward-based care with a view to palliate if the further dete-
Wuhan, China.15 In this report, the patient was known to have rioration was in the patients’ best interests. These decisions were
atrial fibrillation and was treated with rivaroxaban. The acute not easy to make, especially as it was on the first day of presen-
inflammatory state COVID-19 is known to produce had the tation. This decision was made in the context of the patients’
potential to create a prothrombotic environment, culminating in comorbidities, including COPD, the patients’ age, and the avail-
an ischaemic stroke. ability of intensive care beds during the steep rise in intensive care
Some early case studies produced in Wuhan describe patients admissions, in the midst of the COVID-19 pandemic (figure 1).
in the sixth decade of life that had not been previously noted Furthermore, the patients’ rapid and permanent decline in GCS,
to have antiphospholipid antibodies, contain the antibodies entwined with the severe stroke on CT imaging of the brain
in blood results. They are antibodies signify antiphospholipid made it more unlikely that significant and permanent recovery
syndrome; a prothrombotic condition.16 This raises the hypoth- could be achieved from mechanical intubation, especially as the
esis concerning the ability of COVID-19 to evoke the creation damage caused by the stroke could not be significantly reversed.
of these antibodies and potentiate thrombotic events, such as As hospitals manage patients with COVID-19 in many parts of
ischaemic stroke. the world, there may be tension between the need to provide
No peer-reviewed studies on the effects of COVID-19 and higher levels of care for an individual patient and the need
mechanism of stroke are published as of April 2020; therefore, to preserve finite resources to maximise the benefits for most
it is difficult to evidence a specific reason as to why COVID-19 patients. This patient presented during a steep rise in intensive
patients are developing neurological signs. It is suspected that a care admissions, which may have influenced the early decision
mixture of the factors mentioned above influence the develop- not to treat the patient in an intensive care setting. Retrospec-
ment of ischaemic stroke. tive studies from Wuhan investigating mortality in patients with
4 Basi S, et al. BMJ Case Rep 2020;13:e235920. doi:10.1136/bcr-2020-235920
 New disease

BMJ Case Rep: first published as 10.1136/bcr-2020-235920 on 24 August 2020. Downloaded from http://casereports.bmj.com/ on June 4, 2024 by guest. Protected by copyright.
multiple organ failure, in the setting of COVID-19, requiring permits others to distribute, remix, adapt, build upon this work non-commercially,
intubation have demonstrated mortality can be up to 61.5%.17 and license their derivative works on different terms, provided the original work
is properly cited and the use is non-commercial. See: http://creativecommons.org/
The mortality risk is even higher in those over 65 years of age licenses/by-nc/4.0/.
with respiratory comorbidities, indicating why this patient was
unlikely to survive an admission to the intensive care unit.18 ORCID iD
Regularly updating the patients’ family ensured coopera- Saajan Basi http://orcid.org/0000-0002-7441-6952
tion, empathy and sympathy. The patients’ stroke was not seen
as a priority given the severity of his COVID-19 pneumonia,
therefore the least invasive, but most appropriate treatment was
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